Endocytosis and degradation of asialo-glycoprotein were investigated in hepatocytes from carcinogen-treated rats. The cells were isolated at an early stage of carcinogenesis after a sequential treatment with diethylnitrosamine and 2-acetylaminofluorene. Hepatocytes at this pre-nodular stage take up asialo-orosomucoid at a lower rate than hepatocytes from normal rats, whereas degradation of the protein occurs at a similar rate in the two populations. The lower rate of uptake appears to result from a decreased binding capacity in treated hepatocytes. The reduced binding capacity leads to slower kinetics of cell attachment to a substratum of asialo-glycoprotein. The lower number of receptors did not seem to be confined to a particular subpopulation of hepatocytes. Diploid and tetraploid hepatocytes, isolated by centrifugal elutriation, displayed the same reduction in binding capacity.
References
1.
1. Baenziger J and Fiete D (1980). Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes. Cell22:611–620.
2.
2. Evarts RP, Marsden E, Hanna P, Wirth PJ, and Thorgeirsson SS (1984). Isolation of preneoplastic rat liver cells by centrifugal elutriation and binding to asialofetuin. Cancer Res.44:5718–5724.
3.
3. Evarts RP, Marsden ER, and Thorgeirsson SS (1985). Modulation of asialoglycoprotein receptor levels in rat liver by phenobarbital treatment. Carcinogenesis6:1767–1773.
4.
4. Farber E (1984). The multistep nature of cancer development. Cancer Res.44:4217–4223.
5.
5. Gjessing R and Seglen PO (1980). Adsorption, simple binding and complex binding of rat hepatocytes to various in vitro substrata. Exp. Cell Res.129:239–249.
6.
6. Howard DJ, Stockert RJ, and Morell AG (1982). Asialoglycoprotein receptors in hepatic regeneration. J. Biol. Chem.257:2856–2858.
7.
7. Marshall JS, Williams S, Jones P, and Hepner GW (1978). Serum desialylated glycoproteins in patients with hepatobiliary dysfunction. J. Lab. Med.92:30–37.
8.
8. Scatchard G (1949). The attractions of proteins for small molecules and ions. Ann. N.Y. Acad. Sci.50:600–672.
9.
9. Scherer E (1984). Neoplastic progression in experimental hepatocarcinogenesis. Biochim. Biophys. Acta738:219–236.
10.
10. Schulte-Hermann, R, Ohde G, Schuppler J, and Timmerman-Trosiener I (1981). Enhanced proliferation of putative preneoplastic cells in the rat liver following treatment with the tumor promoters phenobarbital, hexachlorocyclohexane, steroid compounds and nafenopin. Cancer Res.41:2556–2562.
11.
11. Schulte-Hermann, R, Roome N, Tummermann-Trosiener I, and Schuppler J (1984). Immunocytochemical demonstration of a phenobarbital-inducible cytochrome P450 in putative preneoplastic foci of rat liver. Carcinogenesis5:149–153.
12.
12. Schwartz AL, Rup D, and Lodish HF (1980). Difficulties in the quantitation of the asialoglycoprotein receptor in rat hepatocytes. J. Biol. Chem.255:9033–9036.
13.
13. Schwarze PE, Pettersen EO, and Seglen PO (1986). Characterization of hepatocytes from carcinogen-treated rats by two-parametric flow cytometry. Carcinogenesis7:171–173.
14.
14. Schwarze PE, Pettersen EO, Shoaib MC, and Seglen PO (1984). Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis. Carcinogenesis5:1267–1275.
15.
15. Schwarze PE, Pettersen EO, Tolleshaug H, and Seglen PO (1986). Isolation of carcinogen-induced, diploid hepatocytes by centrifugal elutriation. Cancer Res.46:4732–4737.
16.
16. Schwarze PE and Seglen PO (1985). Reduced autophagic activity, improved protein balance and enhanced in vitro survival of hepatocytes isolated from carcinogen-treated rats. Exp. Cell Res.157:15–28.
17.
17. Schwarze PE, Tolleshaug H, and Seglen PO (1985). Uptake and degradation of asialo-orosomucoid in hepatocytes from carcinogen-treated rats. Carcinogenesis6:777–782.
18.
18. Seglen PO (1976). Preparation of isolated rat liver cells. Meth. Cell Biol.13:29–83.
19.
19. Seglen PO, Schwarze PE, and Sáter G (1986). Changes in cellular ploidy and autophagic responsiveness during rat liver carcinogenesis. Toxicol. Pathol, (in press).
20.
20. Stockert RJ and Becker FF (1980). Diminished hepatic binding protein for desialylated glycoprotein during chemical hepatocarcinogenesis. Cancer Res.40:3632–3634.
21.
21. Tolleshaug H (1981). Binding and internalization of asialo-glycoproteins by isolated rat hepatocytes. Int. J. Biochem.13:45–51.
22.
22. Tolleshaug H, Abdelnour M, and Berg T (1980). Binding of concanavalin A to isolated hepatocytes and its effect on uptake and degradation of asialofetuin by the cells. Biochem. J.190:697–703.
23.
23. Tolleshaug H, Berg T, Nilsson M, and Norum KR (1977). Uptake and degradation of asialo-fetuin by isolated rat hepatocytes. Biochim. Biophys. Acta499:73–84.
24.
24. Weigel PH and Oka J A (1983). The surface content of asialoglycoprotein receptors in isolated hepatocytes is reversibly modulated by changes in temperature. J. Biol. Chem.258:5089–5094.
25.
25. Williams GM, Klaiber M, Parker SE, and Farber E (1976). Nature of early appearing, carcinogen-induced liver lesions resistant to iron accumulation. J. Natl. Cancer Inst.57:157–161.
